1. Field Invention
This invention relates to microporous membranes, and more particularly to anionic charge modified microporous membranes suitable for the filtration of aqueous fluids, such as biological liquids and for plasmapheresis.
2. Prior Art
Microporous membranes are well known in the art. For example, U.S. Pat. No. 3,876,738 to Marinaccio et al (1975) describes a process for preparing a microporous membrane, for example, by quenching a solution of a film forming polymer in a nonsolvent system for the polymer. European Patent Application No. 0 005 536 (1979) and U.S. Pat. No. 4,340,479 both to Pall describe a similar process.
Other processes for producing microporous membranes are described, for example, in the following U.S. Patents:
U.S. Pat. No. 3,642,668 to Bailey et al (1972); PA0 U.S. Pat. No. 4,203,847 to Grandine,II (1980); PA0 U.S. Pat. No. 4,203,848 to Grandine,II (1980); and PA0 U.S. Pat. No. 4,247,498 to Castro (1981).
Commercially available microporous membranes, for example, made of nylon, are available from Pall Corporation, Glen Cove, N.Y. under the trademark ULTIPOR N.sub.66. Another commercially significant membrane made of polyvinylidene fluoride is available from Millipore Corp., Bedford, Mass. under the trademark DURAPORE. This membrane is probably produced by the aforementioned Grandine,II patents. Such membranes are advertised as useful for the sterile filtration of pharmaceuticals, e.g. removal of microorganisms.
Various studies in recent years, in particular Wallhausser, Journal of Parenteral Drug Association, June 1979, Vol. 33 #3, pp. 156-170, and Howard et al, Journal of the Parenteral Drug Association, March-April, 1980, Volume 34, #2 pp. 94-102, have reported the phenomena of bacterial break-through in filtration media, in spite of the fact that the media had a low micrometer rating. For example, commercially available membrane filters for bacterial removal are typically rated as having an effective micrometer rating for the microreticulate membranes structure of 0.2 micrometers or less, yet such membranes typically have only a 0.357 effective micrometer rating for spherical contaminant particles, even when rated as absolute for Ps. diminuta, the conventional test for bacterial retention. Thus passage of few microorganisms through the membrane may be expected under certain conditions and within certain limits. This problem has been rendered more severe as the medical uses of filter membranes increases. Brown et al highlights this problem in CRC Critical Reviews in Environment Control, March 1980, page 279 wherein increased patient mortality and morbidity derived from contamination of sterile solutions for topical, oral, and intravenous therapy are reported.
One method of resolving this problem and its inevitable consequences, is to prepare a tighter filter, i.e. one with a sufficiently small effective pore dimension to enable the capture of the fine particulate, e.g., microorganisms, by mechanical sieving. Such filter structures, in the form of microporous membranes of 0.1 micrometer rating or less, may be readily prepared. The flow rate, however, exhibited by such structures at conventional pressure drops is low. Thus such modification of the internal geometry, i.e. pore size, of the microporous membrane is not an economical solution to the problem of bacterial breakthrough.
Attempts to increase the short life of filter media due to pore blockage and enhance flow rates through filter media having small pores have been made by charge modifying the media by various means to enhance capture potential of the filter. For example, U.S. Pat. Nos. 4,007,113 and 4,007,114 to Ostreicher, describes the use of a melamine formaldehyde cationic colloid to charge modify fibrous and particulate filter elements; U.S. Pat. No. 4,305,782, to Ostreicher et al describes the use of an inorganic cationic colloidal silica to charge modify such elements; and U.S. Ser. No. 164,797 filed June 30, 1980, to Ostreicher et al, describes the use of a polyamido-polyamine epichlorhydrin cationic resin to charge modify such filter elements. Similar attempts at cationic charging of filter elements were made in U.S. Pat. Nos. 3,242,073 (1966) and 3,352,424 (1967) to Guebert et al; and U.S. Pat. No. 4,178,438 to Hasse et al (1979).
Cationically charged membranes which are used for the filtration of anionic particulate contaminants are also known in the art. For Example charge modified filter membranes are disclosed in the Assignee's Japanese Pat. No. 923649 and French Pat. No. 7415733. As disclosed therein, an isotropic cellulose mixed ester membrane, was treated with a cationic colloidal melamine formaldehyde resin to provide charge functionality. The membrane achieved only marginal charge modification. Additionally, the membrane was discolored and embrittled by the treatment, extractables exceeded desirable limits for certain critical applications, and the membrane was not thermally sanitizable or sterilizable. Treatment of the nylon membranes prepared by the methods described in U.S. Pat. No. 2,783,894 to Lovell (1957) and U.S. Pat. No. 3,408,315 to Paine (1968) is suggested. Nylon membranes so treated also demonstrate marginal charge modification, high extractables and/or are not thermally sanitizable or sterilizable.
Assignee in order to solve the aforementioned problems has developed unique cationic charge modified microporous membranes for use in the filtration of fluids. These cationic membranes, their preparation and use are described and claimed in U.S. patent application Ser. No. 268,543, filed on May 29, 1981 in the name of Barnes et al, now U.S. Pat. No. 4,473,475 and EPC Pub. Nos. 0066 814, and U.S. patent application Ser. No. 314,307, filed on Oct. 23, 1981 in the name of Ostreicher et al, now U.S. Pat. No. 4,473,475 and EPC Pub. Nos. 0050 864.
Cationic charge modified nylon membranes covered by these inventions are now being sold by AMF CUNO Division under the trademark ZETAPOR. Pall Corp., Glen Cove, N.Y. is also selling a cationic charge modified nylon membrane under trademark N.sub.66 POSIDYNE.
To Applicant's knowledge, prior to this invention, no one has produced a useful anionically charged microporous filter membrane for the removal of fine charged particulates from liquids nor has anyone used charge modified microporous filter membrane for cross-flow filtration.
There are numerous references which describe the treatment of reverse osmosis, ultrafiltration, semipermeable type membranes for various objects. See for example, U.S. Pat. Nos. 3,556,305 to Shorr (1971), 3,556,992 to Massuco (1971), 3,944,485 (1976) and 4,045,352 (1977) to Rembaum et al, 4,005,012 to Wrasidlo (1977), 4,125,462 to Latty (1978), 4,214,020 to Ward et al (1980), and 4,239,714 to Sparks et al (1980). Membranes have also been treated to produce anionic ultrafiltration, reverse osmosis, semipermeable type membranes. For example, see the following U.S. Patents:
U.S. Pat. No. 3,004,904 to Gregor (1961) describes an electronegative selective permeable membrane cast from a mixture of a film forming polymer and a substantially linear electronegative polyelectrolyte. Preferably, the membrane is a mixture of a polyvinyl-type resin and a water soluble substantially linear polyvinyl-type polyelectrolyte film. The film is produced by casting an organic solvent solution of the polymer and polyelectrolyte. A number of polyelectrolytes are listed including polyacrylic acid and "carboxylic acid groups".
U.S. Pat. No. 3,524,546 to Hoehn et al, (1970) describes permeation membranes of graft copolymers of nylon produced by grafting at least 300 titratable acid groups on to the polymer chain per million grams of polymer. A preferred material for grafting onto the polymer is polymerizable organic acid, e.g. acrylic acid. A sufficient amount of grafting is said to be when the graft copolymer shows a grafted weight gain of acrylic acid of about 3%. The only methods described for performing such grafting are by high energy ionizing radiation or by the action of free radical generating catalysts. In Example 1, a nylon film was grafted by swelling the film with acrylic acid and then subjecting the film to radiation under an electron beam. The grafted membranes are said to be physically strong, having exceptionally advantageous throughput rates when compared to known permeation membranes.
U.S. Pat. No. 3,672,975 to Arons (1972) describes the copolymerization of polyacrylic acid within a nylon structure. The copolymer is said to have excellent enhanced properties suitable for textile applications, e.g. high moisture sorption, and high melting point. Prior to Arons, in order to form such nylon structures acrylic acid monomer was diffused into the nylon structure and caused to homopolymerize and to graft to the nylon simultaneously. It was also known, prior to Arons, to chemically combine a surface finish of completely polymerized polyacrylic acid to nylon by means of heat curing. Arons improves on these known processes by using a preformed polymer of acrylic acid and copolymerizing it within the nylon structure. The process is accomplished by diffusing the preformed polyacrylic acid under certain prescribed conditions, e.g. pH of 1.5 to 3.5, 1 to 5 hours and 80.degree. to 150.degree. C. Arons indicates that the polyacrylic acid appears to attach to the terminal amine groups of the nylon.
U.S. Pat. No. 3,752,749 to Gregor, (1973) describes the use of cation- and anion-exchange membranes for the electrodialytic concentration and removal of acids from aqeuous effluents. The cation exchange membrane is described as " . . . a homogeneous sheet of insoluble ionexchange material containing sulfonic acid groups or supporting matrix impregnated with a similar material."
U.S. Pat. Nos. 3,808,305 (1974) and 4,012,324 (1977) to Gregor describes a fixed charged (negative or positive) membrane prepared by casting a solution which includes a matrix polymer, a polyelectrolyte and a cross-linking agent to form a film. The membrane is useful for ion exchange membranes, electrodialysis, ultrafiltration, etc. Suitable matrix polymers include nylon 6 and nylon 66. The only polyelectrolytes listed are sulfonic acid polyelectrolytes such as polystyrene sulfonic acid, the sodium salt of polystyrene sulfonic acid, sulfonated polymethyl styrene, and copolymers thereof with other vinyl monomers, polyvinyl sulfonic acid, sulfonated polyvinyl naphthalenes, sulfonated polyvinyl anthracenes, sulfonated linear phenol formaldehyde resins, condensation polyamides and polyesters containing comonomers such as sulfoisophthalic acid salts.
U.S. Pat. No. 4,033,817 to Gregor (1977) describes pressure-driven enzyme coupled membranes composed of a polymeric matrix cast from an interpolymer mixture which includes " . . . polystyrenesulfonic acid (to) provide for a higher polar negative charge within the membrane, and can be used together with a coupling agent such as polyacrylic acid." The homopolymers and copolymers of maleic anhydride may also be included in the interpolymer mixture.
U.S. Pat. No. 4,214,020 to Ward et al (1980) is directed to coating the exteriors of hollow fiber semipermeable membranes. The coatings provide the desired selective separation and/or desirable flux. The process described in Ward et al involves immersing a bundle of hollow fibers in a coating liquid containing materials suitable for forming the coating and providing a sufficient pressure drop from the exterior of the hollow fiber. Material suitable for forming the coating should have a sufficiently large molecular size or particle size so that the material does not readily pass through the pores in the walls of the hollow fibers when subjected to the pressure drop used in the process. The pores in the hollow fibers are said to have an average cross-sectional diameter less than about 20,000 angstroms, and preferably less than about 1000 to 5000 angstroms. Nylon is a material of choice for the hollow fibers. The depositable material may be a poly(alkyl acrylates) and poly(alkyl methacrylates) wherein the alkyl groups have, say 1 to about 8 carbons.
U.S. Pat. No. 4,250,029 to Kiser et al (1981) is directed to coated membranes having two or more coatings of polyelectrolytes with oppositely charged adjacent pairs separated by a layer of material which substantially prevents charge neutralization. The membranes coated are ultrafiltration, reverse osmosis and electrodialysis filtration membranes. Preferred membranes are said to be aliphatic and aromatic nylons. The anionics useful are said to be polymeric anionic polyelectrolytes of relatively high molecular weight, i.e. above 50,000 preferably above 500,000. Kiser et al states that since the anionics are preferably applied as a final coating, after the cationic and on the same side of the membrane as the coatings, there is no essential requirement that the anionic be substantive to the membrane, i.e., the opposite charge of the previously applied cationic coating is sufficient to bind the anionic polyelectrolyte. However, when both the cationic and anionic polyelectrolyte coatings are to be applied to the same side of a membrane they may be separated by a nonionic or neutral layer which may be deposited in the same manner as the polyelectrolytes. This neutral layer separates the oppositely charged polyelectrolyte coating preventing neutralization of the charges. Among specific polyelectrolytes having an anionic charge is poly(acrylic) acid. It is stated, however, that when a coating of cationic material is followed by an anionic layer with little or no neutral layer between the charged layers, the permeation properties of a hollow fiber membrane seems to decrease, as compared to a single layer coating.